Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs

Abstract

Bone has long been acknowledged as a fundamental structural entity that provides support and protection to the body’s organs. However, emerging research indicates that bone plays a crucial role in the regulation of systemic metabolism. This is achieved through the secretion of a variety of hormones, cytokines, metal ions, extracellular vesicles, and other proteins/peptides, collectively referred to as bone-derived factors (BDFs). BDFs act as a medium through which bones can exert targeted regulatory functions upon various organs, thereby underscoring the profound and concrete implications of bone in human physiology. Nevertheless, there remains a pressing need for further investigations to elucidate the underlying mechanisms that inform the effects of bone on other body systems. This review aims to summarize the current findings related to the roles of these significant modulators across different organs and metabolic contexts by regulating critical genes and signaling pathways in vivo. It also addresses their involvement in the pathogenesis of various diseases affecting the musculoskeletal system, circulatory system, glucose and lipid metabolism, central nervous system, urinary system, and reproductive system. The insights gained from this review may contribute to the development of innovative therapeutic strategies through a focused approach to bone secretomes. Continued research into BDFs is expected to enhance our understanding of bone as a multifunctional organ with diverse regulatory roles in human health.

Keywords

Biological Sciences / Biochemistry and Cell Biology

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Funding

National Natural Science Foundation of China (National Science Foundation of China)(82430078, 82261160395, 82230081)

the SMART Grant (B2402033), the Shenzhen Fundamental Research Program (JCYJ20220818100617036), the National Key Research and Development Program of China Grants (2019YFA0906004), the Guangdong Provincial Science and Technology Innovation Council Grant (2017B030301018), and the Shenzhen Key Laboratory of Cell Microenvironment Grant (ZDSYS20140509142721429)

Shenzhen Medical Research Funds (C2401029)

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